mAb Mixtures and Cancer

Need for Simultaneous Multi-targeting

Attempting to therapeutically shut down a tumor cell signaling pathway on a single tumor cell may not be enough when dealing with most cancers. When one pathway is blocked, cancer cells may adapt and become dependent on alternate pathway(s) or other cancer cells may continue to grow and become dominant over time due to different dependencies. In essence it is often the case that mechanisms other than those directly targeted become the drivers of a tumor's resistance to current therapy. New approaches are needed that simultaneously target multiple cell signaling pathways and multiple cell types to increase the chance of significant clinical benefit.

Multi-targeting by mAb Mixtures

The mAb mixture approach enables Symphogen to develop truly innovative and differentiated products, each simultaneously directed against multiple biological targets. We believe that successfully attacking multiple targets and cells with different dependencies, such as tumor cells, stromal cells, immune cells, and/or ligands, provide mAb mixtures with the advantages of greater efficacy and the ability to prevent tumor resistance associated with tumor heterogeneity and adaptability.

Unique Mechanism of Action with mAb Mixtures

Symphogen's research has shown that new and unique mechanisms of action can be obtained with carefully selected mAb mixtures against cancer targets. The Sym004 mAb mixture targeting a receptor tyrosine kinase (EGFR) is one such example where synergistic action of two mAbs cause extensive receptor cross-linking on the cell, while also inducing secondary effector functions to a much greater extent than seen with monoclonal antibodies. Such antibody induced cross-linking of the receptors leads to very efficient internalization of the receptors and subsequent receptor elimination. As a consequence, tumor growth dependent on the receptor targeted by Sym004 is effectively shut down. Symphogen has shown that receptor elimination leads to sustained tumor suppression in a broad range of receptor-dependent animal tumor models superior to that of existing monoclonal antibodies. Receptor elimination by Sym004 has been well-documented in preclinical models and confirmed in ongoing clinical trials.